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dc.contributor.authorRuiz-Pinto, Saraen
dc.contributor.authorPita, Guillermoen
dc.contributor.authorPatiño-García, Anaen
dc.contributor.authorAlonso, Javieren
dc.contributor.authorPérez-Martínez, Antonioen
dc.contributor.authorCartón, Antonio Jen
dc.contributor.authorGutiérrez-Larraya, Federicoen
dc.contributor.authorAlonso, María Ren
dc.contributor.authorBarnes, Danielen
dc.contributor.authorDennis, Joeen
dc.contributor.authorMichailidou, Kyriakien
dc.contributor.authorGómez-Santos, Carmenen
dc.contributor.authorThompson, Deborahen
dc.contributor.authorEaston, Douglasen
dc.contributor.authorBenítez, Javieren
dc.contributor.authorGonzález-Neira, Annaen
dc.date.accessioned2018-04-06T06:56:33Z
dc.date.available2018-04-06T06:56:33Z
dc.date.issued2017-12-01en
dc.identifier.issn1744-6872
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/274616
dc.description.abstractOBJECTIVES: Pediatric cancer survivors are a steadily growing population; however, chronic anthracycline-induced cardiotoxicity (AIC) is a serious long-term complication leading to considerable morbidity. We aimed to identify new genes and low-frequency variants influencing the susceptibility to AIC for pediatric cancer patients. PATIENTS AND METHODS: We studied the association of variants on the Illumina HumanExome BeadChip array in 83 anthracycline-treated pediatric cancer patients. In addition to single-variant association tests, we carried out a gene-based analysis to investigate the combined effects of common and low-frequency variants to chronic AIC. RESULTS: Although no single-variant showed an association with chronic AIC that was statistically significant after correction for multiple testing, we identified a novel significant association for G protein-coupled receptor 35 (GPR35) by gene-based testing, a gene with potential roles in cardiac physiology and pathology (P=7.0×10), which remained statistically significant after correction for multiple testing (PFDR=0.03). The greatest contribution to this observed association was made by rs12468485, a missense variant (p.Thr253Met, c.758C>T, minor allele frequency=0.04), with the T allele associated with an increased risk of chronic AIC and more severe symptomatic cardiac manifestations at low anthracycline doses. CONCLUSION: Using exome array data, we identified GPR35 as a novel susceptibility gene associated with chronic AIC in pediatric cancer patients.
dc.description.sponsorshipThis work was supported by the Spanish Association against Cancer (AECC: Asociación Española contra el Cáncer). Human Genotyping lab is a member of CeGen, PRB2-ISCIII and is supported by grant PT13/0001, of the PE I+D+i 2013-2016, funded by ISCIII and FEDER (Fondo Europeo de Desarrollo Regional). Sara Ruiz-Pinto is a predoctoral fellow supported by the Severo Ochoa Excellence Programme (Project SEV-2011-0191).
dc.languageengen
dc.publisherWolters Kluwer
dc.titleExome array analysis identifies GPR35 as a novel susceptibility gene for anthracycline-induced cardiotoxicity in childhood cancer.en
dc.typeArticle
prism.endingPage453
prism.issueIdentifier12en
prism.publicationDate2017en
prism.publicationNamePharmacogenetics and Genomicsen
prism.startingPage445
prism.volume27en
dc.identifier.doi10.17863/CAM.21759
dcterms.dateAccepted2017-07-21en
rioxxterms.versionofrecord10.1097/FPC.0000000000000309en
rioxxterms.versionAM*
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2017-12-01en
dc.contributor.orcidBarnes, Daniel [0000-0002-3781-7570]
dc.contributor.orcidDennis, Joe [0000-0003-4591-1214]
dc.contributor.orcidThompson, Deborah [0000-0003-1465-5799]
dc.contributor.orcidEaston, Douglas [0000-0003-2444-3247]
dc.identifier.eissn1744-6880
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idCancer Research UK (16563)
rioxxterms.freetoread.startdate2018-12-01


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